Autogeny in Aedes aegypti

埃及伊蚊的自体繁殖

• 批准号: 8020955
• 负责人: DAVID W SEVERSON
• 金额: $ 11.14万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-15 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8020955
• 关键词: Address; Aedes; Automobile Driving; Behavior; Biochemical Pathway; Biology; Blood; Candidate Disease Gene; Cessation of life; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 3; Complex; Culicidae; Data; Deltastab; Dengue; Dengue Virus; Developed Countries; Developing Countries; Development; Disease; Disease Outbreaks; Drug resistance; Engineering; Epidemic; Event; Evolution; Experimental Designs; Feeding behaviors; Female; Fingerprint; Fostering; Foundations; Future; Genes; Genetic; Genetic Markers; Genome; Genomics; Goals; Health; Human; Incidence; Individual; Insecticide Resistance; Institutes; Investigation; Knowledge; Libraries; Microsatellite Repeats; Modeling; Molecular; Molecular Genetics; Mosquito Control; Mosquito-borne infectious disease; Outcome; Ovarian Cycles; Oviposition; Parasites; Phenotype; Population; Population Biology; Positioning Attribute; Production; Protocols documentation; Quantitative Genetics; Quantitative Trait Loci; Reporting; Research; Resolution; Services; Shotgun Sequence Assembly; Single Nucleotide Polymorphism; Single-Stranded Conformational Polymorphism; Techniques; Transgenes; Travel; Universities; Vaccines; Vitellogenesis; Whole-Genome Shotgun Sequencing; base; disorder control; disorder prevention; egg; genetic analysis; genome sequencing; genome wide association study; novel; pathogen; physical mapping; positional cloning; prevent; programs; public health relevance; research study; tool; trait; transmission process; vaccine development; vector

DESCRIPTION (provided by applicant): Mosquito-borne diseases present an increasing global human health threat. These diseases reflect a significant resurgence in most developing countries, and also are emerging as clear threats for epidemic outbreaks in developed countries. Many factors contribute to the inability to date to prevent or control these diseases including poor progress in vaccine development, emergence of insecticide resistance in mosquito populations, drug resistance among parasite populations, lack of support in many developing countries for mosquito control programs, and increased global travel. This proposal seeks to initiate investigations on the autogeny trait observed in many mosquito species examined to date; autogenous females are able to produce an egg batch without the typical need for a blood meal as is typical with most female mosquitoes. Understanding the fundamental biology of mosquito populations, and particularly aspects of vitellogenesis, is critical to proposed efforts to utilize novel genetic approaches for controlling mosquito-borne diseases. At present, no knowledge exists on the molecular determinants of autogeny in any mosquito species. The focus of this proposal is the detailed genetic investigation of autogeny in Aedes aegypti as the model mosquito species for rapidly and efficiently uncovering the genetic basis for autogeny. Our long-term goals for these efforts are to eventually uncover genetic mechanisms likely common to autogeny determination in most if not all mosquito species. Aedes aegypti is the primary global vector for dengue virus. Dengue is a threat to >2.5 billion people, with an annual incidence of ~50 million cases and ~500,000 cases of DHF/DSS resulting in ~24,000 deaths per year. The objectives of this proposal are based on the general hypothesis that genes associated with the autogeny phenotype can be identified and isolated by positional cloning techniques. The proposed research will define a strong foundation toward the eventual detailed investigations of the genes determining autogeny and the knowledge obtained from the detailed understanding of the associated biochemical pathways will increase our basic understanding of vitellogenesis in mosquitoes which has implications for predicting vectorial capacity among mosquito populations. This could have several potential applications including transgene constructs that promote altered and disease limiting behaviors that significantly reduce vectorial capacity, development of targeted biopesticides, or identification of biologically relevant antagonists that disrupt behaviors critical to pathogen transmission or survival. The research plan builds upon and enhances the information obtained from the Ae. aegypti genome project to develop the necessary tools toward the eventual complete elucidation of these gene relationships and their phenotypic outcome. The specific aims of the project are to: 1) perform fine-scale genetic mapping to identify regions containing genes that determine the autogeny phenotype in Aedes aegypti and 2) conduct high-resolution, fine-scale physical mapping of an Aedes aegypti BAC library. PUBLIC HEALTH RELEVANCE: Aedes aegypti is the primary vector for dengue virus. No vaccines are available and disease prevention is largely dependent on avoiding contact with infected mosquitoes. The proposed research will provide valuable new information on the biology of this mosquito relating to the ability of some females to produce eggs without obtaining a blood meal.

描述（由申请人提供）：蚊媒疾病对全球人类健康的威胁日益严重。这些疾病反映出在大多数发展中国家卷土重来，也正在成为发达国家流行病爆发的明显威胁。许多因素导致至今无法预防或控制这些疾病，包括疫苗开发进展缓慢，蚊子种群出现杀虫剂耐药性，寄生虫种群耐药，许多发展中国家缺乏对蚊子控制项目的支持，以及全球旅行的增加。本提案旨在对迄今为止在许多蚊子物种中观察到的自生性状进行研究；同大多数雌蚊一样，自体雌蚊能够在不需要吸血的情况下产卵。了解蚊子种群的基本生物学，特别是卵黄形成的各个方面，对于提出利用新的遗传方法控制蚊媒疾病的努力至关重要。目前，对任何一种蚊子的自生性的分子决定因素还不了解。本研究的重点是对埃及伊蚊这一模式蚊种进行详细的自生遗传研究，以便快速有效地揭示自生的遗传基础。我们这些努力的长期目标是最终揭示大多数（如果不是所有）蚊子物种中可能共同的自生决定的遗传机制。埃及伊蚊是登革热病毒的主要全球媒介。登革热对25亿人构成威胁，年发病率约为5000万例，登革出血热/腹泻病每年约50万例，造成约2.4万人死亡。这一建议的目的是基于与自生表型相关的基因可以通过定位克隆技术鉴定和分离的一般假设。该研究将为最终深入研究决定自生的基因奠定坚实的基础，并从对相关生化途径的详细了解中获得的知识将增加我们对蚊子卵黄发育的基本了解，这对预测蚊子种群的媒介能力具有重要意义。这可能有几个潜在的应用，包括转基因构建，促进改变和疾病限制行为，显着降低媒介能力，开发靶向生物农药，或鉴定生物学相关的拮抗剂，破坏对病原体传播或生存至关重要的行为。研究计划建立在并加强了从Ae获得的信息。为埃及伊蚊基因组计划开发必要的工具，以最终完全阐明这些基因关系及其表型结果。该项目的具体目标是：1)进行精细的遗传作图，以确定含有决定埃及伊蚊自生表型基因的区域；2)对埃及伊蚊BAC文库进行高分辨率、精细的物理作图。